Aqueous emulsion and aerosol delivery system using same

ABSTRACT

An aqueous emulsion system containing vesicular structures which provides a delivery system for a variety of active ingredients. The vesicular structures of the emulsion provide a reservoiring or slow-release effect for the active ingredient or for a propellant, enabling an aerosol delivery system to be effective with a very low VOC content.

TECHNICAL FIELD

This application is a Continuation-In-Part of Applicant's co-pendingapplication, Ser. No. 07/584,963, filed Sep. 19, 1990. Now U.S. Pat. No.5,091,111.

This invention relates to the field of aqueous emulsion systems and theuse of such systems for dispensing aerosols from pressurized containersand more particularly to an improved emulsion system which containsvesicle structures that can be used to provide a reservoiring effect forthe propellant component of an aerosol delivery system.

BACKGROUND ART

A vesicular system may be considered as a particular type of emulsionsystem, in which the dispersed or emulsified phase particles are layeredvesicles which are suspended in the continuous phase.

The fact that vesicular systems can be formed and then used to entrapand carry desirable active compounds is well known. Such systems havemost frequently been formed from organic materials of biological originsuch as lipids (see, e.g., U.S. Pat. No. 4,772,471), Vitamin E (U.S.Pat. No. 4,861,580), or steroids (U.S. Pat. No. 4,917,951), and havebeen especially used in the pharmaceutical fields to provide carriersfor biologically active materials.

A method of making, from non-phospho-lipid surfactants, paucilamellarvesicles having a central cavity substantially filled with awater-immiscible oily material is disclosed by U.S. Pat. No. 4,911,928to Wallach, Paucilamellar Lipid Vesicles. The "lipid vesicles" disclosedby this patent are large (500 nm diameter minimum) multilayeredliposome-like structures which are centrifuged (at 10,000-14,000 rpm for15 minutes) out of the system after formation.

The creation of a vesicular dispersion from non-ionic surfactants isdisclosed by U.S. Pat. No. 4,536,324 to Fujiwara et al., NonionicSurfactant Type Vesicle Dispersion, which discloses a vesicle systemformed from non-ionic surfactants such as polyoxethylene castor oilethers or hardened castor oil ethers combined with sorbitan polyestersof long chain fatty acids in water. Conventional mixing means, frommechanical to ultrasonic, are used to form the vesicle dispersion oremulsion. Suggested uses for the dispersion or emulsion are either aloneas a cosmetic cream or lotion or for containing a lipophilic orhydrophilic pharmaceutically active component.

The creation of a vesicle system from a mixture of cationic and anionicsurfactants in water has been reported by Kaler et al. (Science, Sep.22, 1989, p. 1371) Gentle mixing of cetyltrimethyl ammonium tosylate andsodium dodecyl benzene resulted in immediate and spontaneous (nomechanical agitation) generation of vesicles having particle sizesbetween 30 and 80 nm. The vesicles so formed were said to be stable andable to efficiently encapsulate glucose or other solutes.

Many two component systems for the delivery of an aerosol from apressurized container are known. One component of such a system must bea gaseous propellant. The other component is a liquid component, whichcontains the active ingredient to be dispersed, may be comprised ofvarious solvents, or may have an aqueous base with added solvents.

Many propellants currently used (since the use of nonflammablechlorinated fluorocarbons is being limited for environmental reasons)are flammable hydrocarbon gases such as propane, butane, and isobutane.Aqueous systems are preferred for use with such propellants, since sucha system can limit or even obviate the flammability of the propellantphase.

The use of microemulsions in an aerosol system is known. U.S. Pat. No.4,655,959, Preparation of Non-Flammable Aerosol Propellant MicroemulsionSystem, and U.S. Pat. No. 4,536,323, Non-Flammable PropellantMicroemulsion System, both issued to Stopper, disclose an aerosol systemwhich, when shaken in its container, forms an oil-in-watermicroemulsion. This microemulsion structure allows the amount ofpropellant to be increased up to 50% by weight without flammabilityproblems. Stopper's reason for wishing to have a higher level ofpropellant than the 15% to 25% conventional limit for non-flammabilityis his desire to be able to disperse the entire contents of thedispenser.

A countervailing consideration to the desire to incorporate a largeamount of propellant into an aerosol system for efficiency of deliveryis the desire to limit the amount of volatile organic compounds (VOCs)released into the earth's atmosphere. More immediately critical is theneed to reduce the amount of VOCs into the home, for there is concernthat indoor air pollution may sometimes exceed external air pollutionand this is becoming an issue as a potentially health affectingcondition. California, for example, is developing maximum VOCconcentration regulations for different product categories. The proposedlimit for air freshener double phase aerosols is 30%; for insect 15repellents, it is 65%. Analysis of one of the lowest VOC-containingaerosols currently on the market shows a VOC content of 28%.

An article in Aerosol Age ("CARB/Industry Negotiate Consumer ProductRegs.", Jul. 1990, pp. 22-27) has a table showing the differencesbetween the proposed limits and "industry's needs". Industry need forair fresheners and disinfectants are said to be 70%; for dusting aids,35%; for hair sprays, 80%. The present invention appears to offer asystem that can deliver a variety of active ingredients, making ituseable for a wide variety of products, with a total VOC content farbelow the "industry needs".

Which compounds qualify as VOCs will depend on type as well as molecularweight but, in general, organic compounds with fewer than nine carbonatoms are usually considered potential VOCs. Propane, butane, andisobutane are, obviously, VOCs.

Thus a non-flammable aqueous aerosol system that could effectivelydeliver the container contents with a lower, rather than a higher, levelof propellant is highly desirable both for environmental and regulatoryreasons. However, prior art has not only not produced such a system but,as in the Stopper patents, even teaches away from such a possibility.

All aerosol systems require a certain minimum propellant head spacepressure to expel the contents of the container. Propellant head spacepressure is dependent upon the interaction the propellant has with othersubstances in the container.

A container charged with propane alone (no other substances in thecontainer) will exhibit a head space pressure of 100-110 psi (7031gr/sq. cm-7734.1 gr/sq.cm). A container containing water that is thenfilled with propane will exhibit a head space pressure of 110-120 psi(7834.1 gr/sq. cm-8437.2 gr/sq. cm). When alcohol, glycerol, or asurfactant is added to the water, the head space pressure can belowered. A mixture of 66% water, 30% ethanol, and 4% propane willexhibit a head space pressure of 50 psi, which is a near optimum headspace pressure for an aerosol system which will produce a spray. 55 psi(3867 gr/sq. cm) pressure is considered the optimum figure.

A further consideration for an effective aerosol system is the abilityof the system to maintain the desired pressure as the contents and thepropellant are expelled. The alcohol-water-propane system describedabove exhibits progressively decreased head space pressure as thecontents are expelled from an aerosol container with a vapor tap valve.

A desirable aerosol system should thus have the capacity to entrap orreservoir some of the propellant phase and progressively release thepropellant as the contents of the aerosol container are expelled, thusmaintaining a constant-equilibrium head space pressure over most of theusable life of the aerosol container.

SUMMARY DISCLOSURE OF THE INVENTION

The present invention is a unique aqueous emulsion preparation which canbe used for delivering an aerosol composition from a pressurizedcontainer. It is effective in dispensing the entire contents of thecontainer, yet does so with a lower level of propellant and VOCs thanpreviously possible. Total VOC's of the present invention range from 2%to 25%, compared to the current average aerosol VOC levels of 8% to 98%.

This is accomplished by the production, in the liquid component of thesystem, of an emulsion preparation that includes discrete vesicularparticles which are suspended in a continuous phase and kept in stablesuspension by the mixture of surfactant, primary alcohol, andpolyhydroxy alcohol or polyhydroxy alcohol ester chosen. Thecharacterization of the discrete particles of the emulsion preparationas vesicles of an average size of 20-100 nm is indicated by photoncorrelation spectroscopy and confirmed by electron microscopy.

It has been found that such an emulsion preparation can be produced froma combination of non-ionic single- or double-tailed surfactants, primaryalcohol, polyhydroxy alcohol or polyhydroxy alcohol ester, and anorganic, preferably active, ingredient, and that such a system canentrap or provide a reservoiring effect for small linear organicpropellant molecules in the C₃ -C₅ range. The reservoiring effectresulting from increased partitioning of the propellant in theseformulations due to enhanced mutual compatibility reduces the amountand/or the rate of loss of propellant into the gas phase when theformulation is exposed to atmospheric pressure by the opening of thevapor tap. This reservoiring effect functions similarly to an increasedsolubility--more propellant is held within the system and graduallyreleased. This reservoiring equilibrium effect functions to regulatehead space pressure within the pressurized container and prevents thedecrease of head space pressure that would otherwise occur when a vaportap valve is used. The fact that the propellant is reservoired withinthe aqueous phase makes it possible for the system to function properlyover the useful life of the aerosol container with a lower concentrationof propellant rather than a higher one, which might logically beexpected.

BEST MODE FOR CARRYING OUT THE INVENTION

The first step in the preparation of an aqueous aerosol delivery systemaccording to the present invention is the preparation of an aqueousemulsion stage, which is the same as the aqueous component used toproduce the aerosol delivery system.

A non-ionic surfactant or a mixture of non-ionic surfactants is mixedwith a polyhydroxy alcohol or polyhydroxy alcohol ester and a primaryalcohol. A preservative or antimicrobial agent may be added. Then wateris added and the mixture homogenized to form a lamellar or liquidcrystal phase which is thick (viscosity 20-100 cS), translucent andoften exhibits iridescence. An active organic compound, such as afragrance or an insecticide, is then added to the system. Part of thelamellar liquid crystal structure could be converted into multilamellarliposomes. The degree of this conversion depends mainly on the intensityof shear used in homogenization step. Measured rheological propertiessuch as significant elasticity, shear thinning behavior and highviscosity values at low shear rates indicate that the liquid crystalform is suitable for making shampoos, dermal, and cleaning or polishingformulations.

Next the lamellar stage is subjected to sonification, high energyshearing, or other type of energy addition. This produces a stableaqueous emulsion stage with lower viscosity (approximately 10 cS orlower) which is unclouded and transparent.

Three representative formulations of the invention (one of the lamellaror liquid crystal system and two of the vesicular system) werecentrifuged for five hours at 17,000 rpm (102,000 Deg/Sec) at anacceleration of 34,800 g in a Sorvall Superspeed RC2B centrifuge usingan SS34 rotor. None of the formulations showed any phase separation.This behavior indicates a very high stability for both the lamellar andthe vesicular systems, making them suitable for producing products withlong shelf life.

FIGS. 1-3 all show representative TEM photographs selected from overforty sets of photographs from four different formulations. Allphotographs showed, with expected minor variations, the same structuralmakeup of the emulsion and vesicular phases of the invention. Allsamples were rapidly quenched (frozen) to avoid formation of icecrystals. Then the frozen sample was brought to vacuum and fractured.The samples were shadowed with platinum and photographed by TEM.Original TEM photographs were taken as stereo pairs, to be viewed with astereoscope for maximum resolution.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1, taken at a magnification of 40,300, shows the multilamellarliposome structures contained in a representative preparation of thisaqueous emulsion.

FIG. 2, taken at a magnification of 62,000, shows the vesicularstructures, which average 20-100 nm in diameter, present in the aqueousemulsion after it has been subjected to sonification.

FIG. 3, taken of a slightly different but also representativeformulation of the present invention and taken at a magnification of46,500 shows that, while the majority of the vesicular structurespresent in the sonicated aqueous emulsion are between 20 and 100 nm,there are some larger unilamellar vesicular structures present.

FIGS. 4 and 5 are bar graphs showing the results of testing with respectto DEET-containing formulations as described in Example 15 as set forthbelow. More specifically, FIG. 4 illustrates comparison results withrespect to vesicular DEET and DEET solution and FIG. 5 illustratescomparison results with respect to vesicular DEET and DEET aerosol.

According to one aspect of the present invention, the aqueous emulsionstage may be used to form delivery systems for such preparations aspolishes, fragrances, pesticides, insect repellents, cleaning products,dermal treatments, etc.

According to a second aspect of the present invention, the aqueousemulsion stage component is next placed into a pressurizable container,which is then charged with a propellant.

The aqueous aerosol delivery system is comprised of the aqueous emulsionstage component, which is present in between 75% to 98% by weight of thesystem, and a propellant component, present in between 2% to 25% byweight of the system.

The surfactants used to form the aqueous component of the presentinvention are non-ionic surfactants, which may either be of a singletype having double hydrocarbon tails extending from the functional groupor be a pair combination of two different types of surfactants havingsingle hydrocarbon tails extending from their functional groups.Mixtures of such types of surfactants may also be used. Possible"double-tailed" non-ionic surfactants which may be used in the system ofthe present invention are the fatty acid alkanolamides, ethylene oxideadducts of the higher primary alcohols or an ethoxylated amines.Possible "single-tailed" surfactants, which must be used in pairs aresorbitan monooleate, polyoxyethylene (2) oleyl ether, andpolyoxyethylene (20) sorbitan monooleate. While it is usually desirableto use either a double-tailed surfactant or a pair combination ofsingle-tailed surfactants, it is also possible to use both adouble-tailed surfactant and a single-tailed surfactant combination.Such a combination reduces necessary total level of surfactant as wellas providing an opportunity to alter the characteristics of theresulting systems for specific desired features. The surfactants arepresent in the liquid component in concentrations between 0.25% and6.5%.

The primary alcohols used to form the aqueous component of the presentinvention range from ethanol to oleyl alcohol. It appears that a smallquantity of a primary alcohol is essential to produce the reservoiringeffect which characterizes the invention. It is theorized that thisreservoiring effect is produced by the coupling of the propellant intothe membranes of the vesicles.

Alcohols below C₉, however, are themselves volatile organic compounds,so the preferred alcohols of the present invention are linear C₉ -C₁₈(nonyl to oleyl) alcohols, with the most preferred alcohols being theC₁₀ (decanol) and C₁₁ (1-undecanol) alcohols. The primary alcohol ispresent in the aqueous component in concentrations between 0.001% and3.5%.

The polyhydroxy alcohol or polyhydroxy alcohol ester used to form theaqueous emulsion stage component of the present invention is preferablya C₂ -C₆ alcohol compound such as glycerol, ethylene glycol, ordiethylene glycol. The polyhydroxy alcohol esters are preferably C₁₀-C₃₀ polyhydroxy alcohol esters. Mixtures of polyhydroxy alcohols andpolyhydroxy alcohol esters may be used. Polyhydroxy alcohol ethers mayalso be useable. The polyhydroxy alcohol or polyhydroxy alcohol ester ispresent in the aqueous component at concentrations between 0.1% and 6%.

The aqueous component of the present invention may also include apreservative such as methylparaben, present at concentrations between0.1% and 0.5%.

Included in the aqueous emulsion phase component of the presentinvention is an organic active ingredient chosen according to thedesired characteristics of the final product. Possible organic activeingredients could include fragrances, flavoring agents, pesticides (suchas pyrethrin or linalool) or repellents (including personal insectrepellents such as N, N-diethylamine-meta-toluamide (DEET)), waxes orother polishing agents (including silicone oils), emollients, cleansersor stain removal agents, etc. The active ingredient may be eitherlipophilic or hydrophilic. The organic active ingredient is present inthe aqueous component at concentrations between 0.01% and 20%.

Water makes up the balance of the aqueous component for allformulations. It is preferred that deionized water be used.

The propellant component of the present invention is a linear chainhydrocarbon, such as propane, butane, pentane or mixtures thereof. Thepropellant component is, as discussed above, present at concentrationsbetween 2% and 25% by weight of the total system, and preferably between2% and 10%.

The reservoiring effect of the aerosol system and the need for a longchain alcohol to produce that effect of the present invention is bestillustrated by the behavior of the system with two different propellantgases: isobutane and propane. Propane alone exhibits a head spacepressure of 110 psi. When a non-ionic surfactant, such as a fatty acidalkanolamide, is added to the container, propane exhibits a pressure of96 psi (6749.76 gr/sq. cm). When propane is used as the propellant inthe system of the present invention prepared without a long chainalcohol, the system has a pressure of 100 psi (7031 gr/sq. cm). When along chain alcohol is present in the system, propane pressure is 55 psi,(3867 gr/sq. cm) showing the coupling effect of the alcohol in thesystem with the propellant.

Isobutane alone exhibits a head space pressure of 35 psi (2460.85 gr/sq.cm). When a non-ionic surfactant, such as a fatty acid alkanolamide, isadded to the container, the pressure is 32 psi (2249.92 gr/sq. cm). Whenisobutane is used as the propellant in the system of the presentinvention (with a long chain primary alcohol present), the system has apressure of 39 psi (2742 gr/sq. cm). Isobutane thus appears unable tocouple into the system even in the presence of a long chain primaryalcohol.

It is believed that the reservoiring effect is produced by thepenetration into or coupling with the membranes of the vesicularstructures of the propellant molecules. Propane (as well as butane andn-pentane) molecules, being sterically slender, fit between themolecules of the membrane. Isobutane, however, being sterically morebulky, is unable to fit completely into the vesicular structure in thismanner.

Combinations of non-ionic surfactants, primary alcohols, and polyhydroxyalcohols or polyhydroxy alcohol esters that have been tested and haveproduced stable aerosol systems use components selected from thefollowing groups:

PREFERRED SURFACTANTS Single Surfactants (% concentration range0.25-6.5)

Fatty acid alkanolamide (Monamid 150 ADY)

Linoleamide (Monamid B-442)

Tallow monoethanolamide ethoxylate (Sherex T-55)

Ethylene oxide adducts of nonylphenol (Surfonic N-85, Surfonic N-95,Surfonic N-100)

    ______________________________________                                        Surfactant Pairs                                                              Surfactant 1     Surfactant 2                                                 (% concentration range)                                                                        (% concentrations)                                           ______________________________________                                        Sorbitan monooleate                                                                            Polyoxyethylene (20)                                         (Span 80; 0.5-5.8)                                                                             sorbitan monooleate                                                           (Tween 80; 0.1-5.3)                                          Polyoxyethylene (2) oleyl                                                                      Polyoxyethylene (20)                                         ether (Brij 92; 0.5-6.0)                                                                       sorbitan monooleate                                                           (Tween 80; 0.1-5.3)                                          C.sub.9 -C.sub.11 linear alcohol                                                               Polyoxyethylene (20)                                         ethoxylate       sorbitan monooleate                                          (Neodol 91-2.5; 0.5-6.0)                                                                       (Tween 80; 0.1-5.3)                                          Block copolymer of propylene                                                                   Sorbitan monooleate                                          and ethylene oxide                                                                             (Span 80; 0.1-5.2)                                           (Pluronic L-64; 0.3-5.8)                                                      Fatty acid alkanolamide                                                                        Octylphenoxy polyethoxyethanol                               (Monamid 150 ADY; 0.5-6.5)                                                                     (Triton X-35; 0.2-5.5)                                       Glyceryl laurate Sorbitan monooleate                                          (Kessco 675; 0.3-5.8)                                                                          (Span 80; 0.1-5.2)                                           Linoleamide      Polyoxyethylene (20)                                         (Monamid B-442; 0.5-6.0)                                                                       sorbitan monooleate                                                           (Tween 80; 0.1-5.2)                                          ______________________________________                                    

Preferred Primary Alcohols (% concentration range 0.1-3.1)

CH₃ --(CH₂)₁₀ --OH

Mixed C₉ /C₁₀ /C₁₁ alcohol (Neodol 91)

C₁₁ alcohol (Neodol 1)

CH₃ --(CH₂)11--OH

Mixed C₁₂ /C₁₃ alcohol (Neodol 23)

CH₃ --(CH₂)₁₃ --OH

CH₃ --(CH₂)₁₄ --OH

Mixed C_(l4) /C₁₅ alcohol (Neodol 45)

CH₃ --(CH₂)₁₅ --OH

CH₃ --(CH₂)₁₆ --OH

CH₃ --(CH₂)₁₇ --OH, Oleyl

Preferred Polyhydroxy Alcohols and Polyhydroxy Alcohol Esters (%concentration range 0.1-6.0)

Glycerin, C₃ H₅ (OH)₃

Ethylene glycol, CH₂ OHCH₂ OH

1,2-Propylene glycol, CH₃ CHOHCH₂ OH

Diethylene glycol, CH₂ OHCH₂ OCH₂ CH₂ OH

Glycerol monolaurate, C₁₁ H₂₃ COOCH₂ CHOHCH₂ OH

Glycerol monooleate, C₁₇ H₃₃ COOCH₂ CHOHCH₂ OH

Glycerol monostearate, (C₁₇ H₃₅)COOCH₂ CHOHCH₂ OH

The following examples, all using possible combinations of the necessarycomponents of the invention, are grouped according to their functionaluse. It should be understood that all variations may be used with theappropriate active ingredient to produce products with differentfunctions and slightly different characteristics.

Air Freshener Emulsion and Aerosol Preparations Example 1

1.6 grams of methylparaben (0.2% by weight) and 4.0 grams of ethanol(0.5%), were placed in a 2-liter stainless steel mixing beaker. The twowere hand mixed with a spatula until the methylparaben was completelydissolved.

12 grams of Monamid 150 ADY (fatty acid alkanolamide) (1.5%), 8.0 gramsof glycerol (1%), 0.8 grams of Neodol 1, (1-undecanol, 0.1%), and 2.4grams of IFF fragrance 6673-AP (0.3%) were placed in the mixingcontainer. The contents of the container were hand mixed with a spatulato produce a homogeneous mix.

699.2 grams of deionized water (87.4%) was next placed in the container.Agitation with a Gifford-Wood, Model 1L, homogenizer mixer was initiatedand medium shear utilized to the point (5 minutes) of producing ahomogeneous, thickened liquid, ringing gel. Lamellar layers were presentin the batch at this point and continued to form as the batch stood foran additional couple of hours.

Lamellar or liquid crystal structure was indicated by polarized lightmicroscopy, fluorescent probe analysis, and Frequency Response Analysis(FRA).

205.6 grams of the above lamellar system (91%) was placed in a 400 ml.beaker, which was then subjected to sonification for two minutes using aSonics & Materials, Inc., 600 Watt High Intensity Ultrasonic Processor.Ultrasonic agitation converted the batch to a semi-clear emulsionsolution with a viscosity similar to that of water, a pH of 8.4, and aspecific gravity of 0.9909. Fluorescent probe analysis and FRA indicatedthe presence of vesicles.

Example 2

A formulation made up according to the procedure of Example 1 with 3%Monamid 150 ADY, 0.1% Neodol 1, 1% glycerol, and 0.3% fragrancewas--before sonification--photographed by TEM as described before.

FIG. 1 (40,300 magnification) shows the multilamellar liposomestructures present in the lamellar phase of this formulation.

FIG. 2 (62,000 magnification), taken after sonification of the lamellarphase, shows the presence of many vesicular structures of an averagesize of 20-100 nm in the emulsion. Some larger unilamellar vesicles arealso present.

Preparation of the pressurized air freshener containing aerosolcontainer

205.6 grams (91%) of the intermediate described above was placed in a305 cc. metal can, and a standard dip tube, push-activated vapor tapaerosol valve (Precision Valve Corp. Stem 0.024", vapor tap 0.013") wascrimped on. The can was evacuated to 20 inches (50.8 cm) of vacuum. Thecan was then pressure filled with 36 ml. (20.2 grams, 9%) of apropellant blend consisting of 33% A-108 propane and 67% of A-17 butane.The aerosol can was held at 130° F. for 20 minutes in a hot tank, andthe pressure was checked with a hand held pressure gauge (Liquid Filled,U.S. Gauge, 0-160 psi) and found to be 120 psi. The can was then cooledto 72° F. (22.2° C.). The finished product was found to have a pressureof 54 psi (3796.74 gr/sq. cm).

Example 3

A formulation made up according to the procedure of Example 1 but using1.5% Monamid 150 ADY, 0.1% Neodol 1, 1% glycerol, 0.3% fragrance, 88.10%distilled water and 9% of the propane-butane blend produced a stable,semi-clear liquid phase aerosol system having a pressure of 56 psi(3937.36 gr/sq. cm), while increasing the Monamid level to 6.5% producedan aerosol system having a pressure of 55 psi (3867 gr/sq. cm).Increasing the level of glycerol to 6% produced a system with a pressureof 53 psi (3867 gr/sq. cm).

Example 4

A formulation made up according to the procedure of Example 1 but using2% Monamid 150 ADY, 0.2% methylparaben, 0.5% ethanol, 1% glycerol, 0.3%fragrance, 90% deionized water, 3% n-pentane, and 3% propane produced anaerosol system with a pressure of 55 psi (3867 gr/sq. cm).

Example 5

A formulation similar to that of Example 3 but with 6% n-pentane and 3%propane (and 87% water) produced a system with a pressure of 37 psi(2601.47 gr/sq. cm), lower than the ideal pressure for aerosols intendedto produce sprays but appropriate for aerosols intended to deliver suchproducts as post-delivery foaming gels.

Example 6

As discussed before, the non-ionic surfactant of the aqueous componentneed not be of a single type. It can be a combination of two types ofnon-ionic surfactants that interact to produce the vesicular structureof the system.

A formulation made up according to the procedure of Example 1 but using1.5% Span 80 (sorbitan monooleate), 0.3% Tween 80 (polyoxyethylene (2)oleyl ether), 0.25% Neodol 1, 1% glycerol, 0.3% fragrance, 88.35%distilled water, and 9% of the propane-butane blend produced an aerosolsystem having a pressure of 54 psi (3796.74 gr/sq. cm).

Example 7

A formulation made up according to the procedure of Example 1 but using2.5% Monamid 150 ADY, 0.2% methylparaben, 0.1% Neodol 1, 1% ethyleneglycol, 0.3% fragrance, 87.1% deionized water, and 9% of thepropane-butane blend, produced an aerosol system with a pressure of 55psi (3867. gr/sq. cm).

Example 8

A formulation made up according to the procedure of Example 1 but using2.5% Monamid 150 ADY, 0.1% Neodol 1, 1% glycerol monooleate, 0.3%fragrance, 87.1% distilled water and 9% of the propane-butane blendproduced a stable, semi-clear liquid phase aerosol system having apressure of 53 psi (3726.43 gr/sq. cm).

Insecticide Emulsion and Aerosol Preparation Example 9

1.6 grams of methylparaben (0.2%) and 4.0 grams of ethanol (0.5%) wereplaced in a 2-liter stainless steel mixing beaker. The two were handmixed with a spatula until the methylparaben was completely dissolved.

16 grams of Monamid 150 ADY (2%), 12.0 grams of glycerol (1.5%), and 1.6grams of 2,2,4-trimethyl pentane (0.2%) were next placed in the mixingcontainer. The contents of the container were hand mixed with a spatulato produce a homogeneous mix.

668.8 grams of deionized water (83.6%) was next placed in the container.Agitation with a Gifford-Wood, Model 1L, Homogenizer mixer was initiatedand medium shear utilized to the point (5 minutes) of producing ahomogeneous, thickened liquid, ringing gel. Lamellar layers were presentin the batch at this point and continued to form as the batch stood foran additional couple of hours.

Lamellar, liquid crystal structure was indicated by polarized lightmicroscopy, fluorescent probe analysis, and FRA.

8 grams of pyrethrum extract (Aerosol grade 20% Pyrethrins) (3%) wereplaced in the container, and the gel was then sheared for 5 minutes toform a homogeneous, milky white, lamellar system.

207.4 grams (91%) of the above lamellar system was placed in a 400 ml.beaker, which was then subjected to sonification for two minutes using aSonics & Materials, Inc., 600 Watt (2047.74 BTU/Hr.) High IntensityUltrasonic Processor. Ultrasonication converted the batch to a milkywhite, emulsion solution with a viscosity similar to water, pH of 8.94,and a specific gravity of 1.0005. Fluorescent probe analysis and FRAindicated the presence of vesicles.

Preparation of the Pressurized Insecticide-Containing Aerosol Container

207.4 grams (91%) of the intermediate described above was placed in a305 cc. metal can, and a vapor tap aerosol valve was crimped on. The canwas evacuated to 20 inches of vacuum. The can was then pressure filledwith 36 ml. (20.2 g, 9%) of a propellant blend consisting of 33% A-108propane and 67% of A-17 butane. The aerosol can was held at 130° F. (54°C.) for 20 minutes in a hot tank, and the pressure was checked with ahand held pressure gauge (Liquid Filled, U.S. Gauge 0-160 psi) and foundto be 122 psi (8577.82 gr/sq. cm). The can was then cooled to 72° F.(22.2° C.). The finished product was found to have a pressure of 55 psi(3867 gr/sq. cm).

Insect Repellent Emulsion and Aerosol Preparation Example 10

20 grams of Monamid B-442 (linoleamide) (2.5%), 12.0 grams of glycerol(1.5%) and 2.4 grams of 2,2,4-trimethyl pentane (0.3%) were next placedin the mixing container. The contents of the container were hand mixedwith a spatula to produce a homogeneous mix.

66.8 grams of deionized water (71.7%) was next placed in the container.Agitation with a Gifford-Wood, Model 1L, Homogenizer mixer was initiatedand medium shear utilized to the point (5 minutes) of producing ahomogeneous, thickened liquid, ringing gel. Lamellar layers were presentin the batch at this point and continued to form as the batch stood foran additional couple of hours.

Liquid crystal structure was confirmed by polarized light microscopy,fluorescent probe analysis and FRA.

120 grams of DEET (15%) were placed in the container, and the gel wasthen sheared for 5 minutes to form a homogeneous, milky white, lamellarsystem.

728 grams of the above batch was placed in a 400 ml. beaker, which wasthen subjected to sonification for two minutes using a Sonics &Materials, Inc., 600 Watt High Intensity Ultrasonic Processor.Ultrasonication converted the batch to a milky white, vesicular solutionwith a viscosity similar to water, pH of 8.94, and a specific gravity of1.0005. Fluorescent probe analysis and FRA indicated the presence ofvesicles.

Preparation of the Pressurized Insect Repellent-Containing AerosolContainer

728 grams of the intermediate described above was placed in a 305 cc.metal can, and a vapor tap aerosol valve was crimped on. The can wasevacuated to 20 inches (50.8 cm) of vacuum. The can was then pressurefilled with 36 ml. of a propellant blend consisting of 33% A-108 propaneand 67% of A-17 butane. The aerosol can was held at 130° F. (54° C.) for20 minutes in a hot tank, and the pressure was checked with a hand heldpressure gauge (Liquid Filled, U.S. Gauge 0-160 psi) and found to be 122psi (8577.82 gr/sq. cm). The can was then cooled to 72° F. (22.2° C.).The finished product was found to have a pressure of 55 psi (3867 gr/sq.cm).

Dye-Containing Emulsion Preparation Example 11

A formulation was made up according to the procedure of Example 8 butusing 2.5% Monamid 150 ADY, 0.1% Neodol 1, 1.0% glycerol, 0.3%2,2,4-trimethyl pentane, and 0.02% 5(6) carboxy fluorescein. Capturevolumes (CV, defined as the captured volume per gram of surfactant, thesurfactant in this case being considered as including both the primaryalcohol and the other surfactants) were determined using a dialysistechnique (using the carboxy fluorescein as the tracer). The resultswere: CV for the liquid crystal system, 1.9 ml/g; CV for the vesiclesystem, 18.9 ml/g. Thus, the vesicular system is able to entrap and holda large volume of active organic ingredient.

FIG. 3, (46,500 magnification) shows this preparation aftersonification. The vesicular structures visible range from 25 to 300 nm,with most in the 20 to 100 nm range.

Emulsion Cologne Preparation Example 12

A formulation was made up according to the procedure of Example 1 with3.0% tallow monoethanolamide 5.5 mole ethoxylate (Sherex Varamid T55),0.2% dimethicone, 1.5% glycerin, 2.0% fragrance, 0.5% Aerosurf TA-100(distearyl dimethyl ammonium chloride), 0.0001% dye, 1.0% ethanol,0.005% silicon antifoam emulsion (Dow Corning DB-110) and 92.3%deionized water. When fragrance was applied to a user's skin in anethanol control mixture and in the vesicular preparation, the odor ofthe fragrance in the vesicular preparation remained strong longer thanit did in the control mixture (tested at 3 hours after application).

It would appear that, in the same way that the vesicular structuresreservoir and gradually release propellant in an aerosol preparation,they also reservoir and gradually release other active ingredients.

Stain Removing Emulsion Preparation Example 13

A formulation was made up according to the procedure of Example 1 with7.7% C₁₂ -C₁₃ linear primary alcohol ethoxylate (surfonic L24-4). 5% of50% citric acid 3.5% of 50% NaOH, 0.05% silicon antifoam emulsion (DowCorning DB-110), 0.5% propylene glycol in butyl ether (Dowanol PnB),0.7% distearyl dimethyl ammonium chloride, 0.9% glycerin, 2.1% tallowmonoethanolamide 5.5 mole ethoxylate (Sherex Varamide T55), 0.2% Neodol1, 0.1% Barquat 4250 (alkyl dimethyl benzyl ammonium chloride/alkyldimethyl ethyl benzyl ammonium chloride), 0.05% Tinopal CBS-X(distrylbiphenyl derivative), and 80.9% deionized water.

The resulting vesicular preparation when compared to two commerciallyavailable stain removal products, showed improved stain/soil removalproperties with almost all types of stain or soil. The vesicularpreparation is most noticeably superior to currently available productsin the area of oily stains.

Skin Care Emulsion Preparation Example 14

A formulation was made up according to the procedure of Example 1 with12% glycerin, 5% distearyl dimethyl ammonium chloride (Arosurf TA-103),4% petrolatum, 3% isopropyl palmitate, 2.5% cetyl alcohol, 1.25%dimethicone, 0.1% methyl paraben, 0.05% fragrance, 0.04% propyl paraben,and 0.01% sodium chloride, the balance being deionized water.

The resulting vesicular preparation, when compared to a standardemulsion-type skin lotion showed an improved cosmetic feel on the user'sskin being neither greasy nor tacky while imparting a feel of softnessto the skin.

Insect Repellent Preparation Example 15

The fact that the vesicular formulation of the present invention provedto provide a "reservoiring effect" for propellants has been discussed,as has a similar effect with fragrances. It was found that when theactive ingredient added to the vesicle preparation was an insectrepellent (DEET), the resulting preparation showed a more lastingrepellency effect than did a preparation of DEET in ethanol. It wouldappear that the vesicles provide a similar reservoiring effect for theDEET molecules, and that a vesicular DEET preparation prevents rapidevaporation of DEET from a user's skin and provides longer durationprotection.

A formulation was made up according to the procedure of

Example 1 with the following components: 15.0% DEET, 0.2%methylparasept, 0.5% ethanol, 2.8% Monamid B-442, 1.5% glycerine, 0.3%2,2,4-Trimethyl Pentane, and 79.7% deionized water.

This preparation was tested against 1) formulations of DEET in ethanol(14.25% DEET, 0.75% DEET isomers, 85% ethanol) and 2) an aerosolformulation of DEET (14.25% DEET, 0.75% DEET isomers, 10% propellant,75% ethanol). In all cases, the vesicular DEET preparation providedlonger lasting protection against bites from either mosquitoes or stableflies.

Two sets of tests were conducted to determine the relative protectiontimes of this vesicular DEET formulation. Following are the summarizeddata for each test. Tables 1 and 2 show the results of the vesicularDEET formation when compared to a liquid control; Tables 3 and 4 showthe results when an aerosol preparation was used as the control.Included in the summary for each test is a table of the mean protectiontimes, and a table with the Standard Errors of the Means (SEM). FIG. 4shows a bar graph for the results of Test 1 and FIG. 5 shows a bar graphfor the results of Test 2.

                  TABLE 1                                                         ______________________________________                                        Protection Times of Vesicular DEET vs. DEET                                   solution on mosquitoes (M) and stable flies (SF).                                                Mean Protection                                                               Time (in Hours).sup.1                                                DEET   No.     Lands     Bites                                                mg/cm.sup.2                                                                          Reps    M      SF   M    SF                                  ______________________________________                                        Vesicular DEET                                                                            0.23     4       0.38a                                                                              1.00a                                                                              4.38a                                                                              3.88a                             DEET (in EtOH)                                                                            0.23     4       1.25a                                                                              0.75a                                                                              2.25b                                                                              2.25b                             ______________________________________                                         .sup.1 Numbers in columns followed by the same letters are not                significantly different (TTest, α = 0.10).                         

                  TABLE 2                                                         ______________________________________                                        Standard Errors of the Means (SEM) for Table 1.                                           SEMs for Mean Protection Time                                                 Lands           Bites                                             Formulation   M      SF         M    SF                                       ______________________________________                                        Vesicular DEET                                                                              0.24   0.54       0.63 0.63                                     DEET (in EtOH)                                                                              0.52   0.32       0.78 0.32                                     ______________________________________                                    

                  TABLE 3                                                         ______________________________________                                        Protection Times of Vesicular DEET vs. DEET                                   aerosol on mosquitoes (M) and stable flies (SF).                                                 Mean Protection                                                               Time (in Hours).sup.1                                                DEET   No.     Lands     Bites                                                mg/cm.sup.2                                                                          Reps    M      SF   M    SF                                  ______________________________________                                        Vesicular DEET                                                                            0.23     6       0.00b                                                                              1.83a                                                                              4.00a                                                                              5.67a                             DEET (in EtOH                                                                             0.23     6       0.25a                                                                              0.50b                                                                              1.58b                                                                              2.08b                             with propellant)                                                              ______________________________________                                         .sup.1 Numbers in columns followed by the same letters are not                significantly different (TTest, α = 0.10).                         

                  TABLE 4                                                         ______________________________________                                        Standard Errors of the Means (SEM) for Table 3.                                           SEMs for Mean Protection Time                                                 Lands           Bites                                             Formulation   M      SF         M    SF                                       ______________________________________                                        Vesicular DEET                                                                              0.00   0.62       0.98 0.38                                     DEET (in EtOH 0.17   0.26       0.24 0.44                                     with propellant)                                                              ______________________________________                                    

A different formulation, using 0.25% Neodol 1 instead of the ethanol (%water adjusted accordingly), was also made up and had similareffectiveness and properties to the formulation tested.

Other modifications of the aqueous emulsion preparation and of theaerosol delivery system utilizing that preparation of the presentinvention will become apparent to those skilled in the art from anexamination of the above patent Specification and drawings. Therefore,other variations of the present invention may be made which fall withinthe scope of the following claims even though such variations were notspecifically discussed above.

Industrial Applicability

Both the aqueous emulsion preparation and the aerosol delivery system ofthe present invention can be used to deliver many types of products.Active ingredients to be delivered by such systems can include suchthings as pesticides, insect repellents, fragrances, emollients,polymers, and polishing or cleansing compounds, etc.

What I claim is:
 1. An aqueous emulsion system comprising a mixture of anon-ionic surfactant, a C₂ -C₁₈ primary alcohol, a compound selectedfrom the group consisting of polyhydroxy alcohols, polyhydroxy alcoholesters and mixtures thereof, and active ingredient and water, thismixture being processed so as to produce an aqueous emulsion systemcontaining vesicular structures of an average size of 10-300 nm.
 2. Theaqueous emulsion system of claim 1 wherein the mixture comprises anon-ionic surfactant, a C₉ -C₁₈ primary alcohol, a compound selectedfrom the group consisting of a C₂ -C₆ polyhydroxy alcohol, a C₁₀ -C₃₀polyhydroxy alcohol ester and mixtures thereof, an active ingredient andwater.
 3. The aqueous emulsion system of claim 1 wherein the mixturecomprises 0.25% to 6.5% of a non-ionic surfactant, 0.001% to 3.5% of aC₉ -C₁₈ primary alcohol, 0.1% to 6% of a C₂ -C₆ polyhydroxy alcohol, and0.01% to 20% of an organic active ingredient, the balance of theemulsion system being water.
 4. The aqueous emulsion system of claim 1wherein the non-ionic surfactant is a mixture of two or more non-ionicsurfactants.
 5. The aqueous emulsion system of claim 1 wherein thenon-ionic surfactant is a non-ionic surfactant having a pair ofhydrocarbon chains attached to its functional group.
 6. The aqueousemulsion system of claim 1 wherein the non-ionic surfactant is anon-ionic surfactant having a hydrocarbon chain attached to itsfunctional group.
 7. The aqueous emulsion system of claim 1 wherein thenon-ionic surfactant is selected from the group consisting of anethylene oxide adduct of nonyl phenol, a fatty acid alkanolamide, and anethoxylated amine.
 8. The aqueous emulsion system of claim 1 wherein theprimary alcohol is selected from the group consisting of a C₁₀ alcoholor a C₁₁ alcohol.
 9. The aqueous emulsion system of claim 1 additionallycomprising from 0.1% to 0.5% of a preservative.
 10. The aqueous emulsionsystem of claim 1 wherein the mixture comprises 0.25% to 6.5% of a fattyacid alkanolamide surfactant, 0.001% to 3.5% of a C₁₁ primary alcohol,0.1% to 6% of glycerol and 0.01% to 20% of an organic active ingredient,the balance of the emulsion being water.
 11. The aqueous emulsion systemof claim 10 wherein the organic active ingredient is an insectrepellent.
 12. The aqueous emulsion system of claim 10 wherein theorganic active ingredient is an odor-imparting material.
 13. The aqueousemulsion system of claim 10 wherein the organic active ingredient is acleaning and polishing material.
 14. The aqueous emulsion system ofclaim 10 wherein the organic active ingredient is a dermal treatmentmaterial.
 15. The aqueous emulsion system of claim 10 wherein theorganic active ingredient is a stain removal agent.
 16. A method ofpreparing an aqueous emulsion system containing vesicular structures ofan average size of 10-300 nm comprising:placing into a container anon-ionic surfactant, a C₂ -C₁₈ primary alcohol, a compound selectedfrom the group consisting of polyhydroxy alcohols, polyhydroxy alcoholesters and mixtures thereof, and an organic active ingredient, mixingthese ingredients in the container to produce a homogeneous mixture,adding water to the container, further mixing the ingredients in thecontainer to form a lamellar stage, and adding energy, by means ofutilizing a method selected from the group consisting of a high energyshearing and sonification, to the lamellar stage to produce the vesiclecontaining emulsion.
 17. The method of preparing an aqueous emulsionsystem of claim 15 wherein the method comprises:placing into a containera non-ionic surfactant, a C₉ -C₁₈ primary alcohol, a compound selectedfrom the group consisting of a C₂ -C₆ polyhydroxy alcohol, a C₁₀ -C₃₀polyhydroxy alcohol ester and mixtures thereof, and an organic activeingredient, mixing these ingredients in the container to produce ahomogeneous mixture, adding water to the container, further mixing theingredients in the container to form the lamellar stage, and addingenergy, by means of utilizing a method selected from the groupconsisting of a high energy shearing or sonification, to the lamellarstage to produce the vesicle containing emulsion.
 18. The method ofpreparing an aqueous emulsion system of claim 15 wherein the methodcomprises:placing into a container from 0.25 to 6.5% by weight of anon-ionic surfactant, from 0.001% to 3.5% by weight of a C₉ -C₁₈ primaryalcohol, from 0.1% to 6% of a C₂ -C₆ polyhydroxy alcohol, and from 0.01%to 20% of an organic active ingredient, mixing these ingredients in thecontainer to produce a homogeneous mixture, adding water to thecontainer to bring the total weight to 100%, further mixing theingredients in the container to form the lamellar stage, and addingenergy, by means of utilizing a method selected from the groupconsisting of a high energy shearing or sonification, to the lamellarstage to produce the vesicle containing emulsion.
 19. The method ofpreparing an aqueous emulsion system of claim 15 wherein the non-ionicsurfactant is a mixture of two or more non-ionic surfactants.
 20. Themethod of preparing an aqueous emulsion system of claim 15 wherein thenon-ionic surfactant is a non-ionic surfactant having a pair ofhydrocarbon chains attached to its functional group.
 21. The method ofpreparing an aqueous emulsion system of claim 15 wherein the non-ionicsurfactant is a non-ionic surfactant having a hydrocarbon chain attachedto its functional group.
 22. The method of preparing an aqueous emulsionsystem of claim 15 wherein the non-ionic surfactant is a mixture of anon-ionic surfactant having a pair of hydrocarbon chains attached to itsfunctional group and a non-ionic surfactant having a hydrocarbon chainattached to its functional group.
 23. The method of preparing an aqueousemulsion system of claim 15 wherein the non-ionic surfactant is selectedfrom the group consisting of an ethylene oxide adduct of nonyl phenol, afatty acid alkanolamide, and an ethoxylated amine.
 24. The method ofpreparing an aqueous emulsion system of claim 15 wherein the primaryalcohol is selected from the group consisting of a C₁₀ alcohol or a C₁₁alcohol.
 25. The method of preparing an aqueous emulsion system of claim15 wherein the aqueous emulsion additionally comprises from 0.1% to 0.5%of a preservative.
 26. A method of preparing an aqueous emulsion systemcontaining vesicular structures of an average size of 10-300 nmcomprising:preparing a lamellar phase system by: placing into acontainer from 0.25 to 6.5% by weight of a fatty acid alkanolamidesurfactant, from 0.001% to 3.5% by weight of a C₁₁ primary alcohol, from0.1% to 6% of glycerol, and from 0.01% to 20% of an organic activeingredient, mixing these ingredients in the container to produce ahomogeneous mixture, adding water to the container to bring the totalweight to 100%, further mixing the ingredients in the container to forma lamellar stage, and adding energy, by means of utilizing a methodselected from the group consisting of a high energy shearing orsonification, to the lamellar stage to produce the vesicle containingemulsion.
 27. The method of preparing an aqueous emulsion system ofclaim 15 wherein the organic active ingredient is an insect repellentmaterial.
 28. The method of preparing an aqueous emulsion system ofclaim 15 wherein the organic active ingredient is an odor impartingmaterial.
 29. The method of preparing an aqueous emulsion system ofclaim 15 wherein the organic active ingredient is a cleaning andpolishing material.
 30. The method of preparing an aqueous emulsionsystem of claim 15 wherein the organic active ingredient is a dermaltreatment material.
 31. The method of preparing an aqueous emulsionsystem of claim 15 wherein the organic active ingredient is a stainremoval agent.